The system of isolated frog erythrocytes has been used as a model to study the molecular mechanisms of the loss of membrane-bound Beta-adrenergic receptor recognition sites that occurs during receptor desensitization induced by exposure to excessive amount of isoproterenol. We have shown that the decrease in the membrane-bound Beta-receptor recognition sites is associated with an internalization of the surface bound receptors into subcellular structures. A portion of the internalized receptor site is present in a soluble fraction which is devoid of adenylate cyclase activity and guanine nucleotide binding protein. This soluble or internalized receptors bind Beta-receptor agonists with low affinity and this agonist binding is unaffected by guanine nucleotides. Beta-Receptor internalization is energy required and may involve the activity of transglutaminase and lysosomal enzymes. When Beta-receptors are resensitized the internalized receptors appear to be cycled to the plasma membrane. In an attempt to obtain an insight of the detailed mechanisms of Beta-receptor internalization, we have produce a monoclonal antibody to Beta2-receptors of frog erythrocytes using a clone of hybridoma derived from spleen cells of immunized mouse and myeloma P3 x 63.Ag8. This monoclonal antibody directs against a site that is dintinct from the ligand binding site. It also immunoprecipitates internalized Beta-receptor recognition site in frog erythrocytes but this interaction is of relatively low affinity, suggesting that internalized and membrane-bound beta-receptor sites differ in their biochemical properties. We are attempting to produce a library of Beta-receptor monoclonal antibodies in order to elucidate a structural and functional relationship of Beta-adrenergic receptors and to obtain a better understanding of the sequences of events that occur during Beta-receptor internalization.